PUBLICATION

Calycosin attenuates doxorubicin-induced cardiotoxicity via autophagy regulation in zebrafish models

Authors

Lu, X., Lu, L., Gao, L., Wang, Y., Wang, W.

ID

ZDB-PUB-210326-1

Date

2021

Source

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 137: 111375 (Journal)

Registered Authors

Keywords

Autophagy, Calycosin, Cardiotoxicity, Doxorubicin, Zebrafish

MeSH Terms

Doxorubicin/antagonists & inhibitors*
Doxorubicin/toxicity*
Survival Analysis
Zebrafish*
Autophagy/drug effects*
Cardiotonic Agents/pharmacology*
Cardiotoxicity*
Myocardium/pathology
Autophagy-Related Protein 7/drug effects
Heart/drug effects
Isoflavones/pharmacology*
Animals
Heart Function Tests
Antibiotics, Antineoplastic/toxicity*
Embryo, Nonmammalian

(all 15)

PubMed

33761601 Full text @ Biomed. Pharmacother.

Abstract

Anthracyclines are highly effective chemotherapeutics for antineoplastic treatment. However, cumulative cardiotoxicity is the main side effect with poor prognosis. No mechanism-based therapy is currently available to reverse chronic anthracycline-induced cardiotoxicity (AIC) after the deterioration of cardiac function. Calycosin (CA) is the main compound extracted from the traditional Chinese medicine Astragalus, and it has diverse beneficial effects, including autophagy modulation, anti-inflammatory and anti-tumor effects. Autophagy dysregulation is an important pathological event in AIC. Our study demonstrated a cardioprotective effect of CA in a zebrafish embryonic AIC model. To assess the effect of CA on late-onset chronic AIC, adult zebrafish were treated with CA 28 days after doxorubicin (DOX) injection, at which point heart function was obviously impaired. The results demonstrated that DOX blocked autophagic activity in adult zebrafish 8 weeks post-injection, and CA treatment improved heart function and restored autophagy. Further in vitro experiments demonstrated that atg7, which encodes an E1-like activating enzyme, may play an essential role in the CA regulation of autophagy. In conclusion, we used a rapid pharmacological screening system in embryo-adult zebrafish in vivo and elucidated the mechanism of gene targeting in vitro.

Genes / Markers

Figures

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Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
WT	control	Adult	heart	RTPCR	Fig. 3
WT	chemical treatment by injection: doxorubicin	Adult	heart	RTPCR	Fig. 3
WT	chemical treatment by injection: doxorubicin, chemical treatment by environment: calycosin	Adult	heart	RTPCR	Fig. 3
WT	chemical treatment by injection: doxorubicin	Adult	heart	RTPCR	Fig. 2
WT	chemical treatment by injection: doxorubicin, chemical treatment by environment: calycosin	Adult	heart	RTPCR	Fig. 2
WT	standard conditions	Adult	heart	RTPCR	Fig. 2
WT	standard conditions	Adult	heart	RTPCR	Fig. 2
WT	chemical treatment by injection: doxorubicin	Adult	heart	RTPCR	Fig. 2
WT	chemical treatment by injection: doxorubicin, chemical treatment by environment: calycosin	Adult	heart	RTPCR	Fig. 2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: bafilomycin A1	Adult	cardiac ventricle Ab11-map1lc3 labeling increased amount, abnormal	Fig. 3
WT	chemical treatment by environment: doxorubicin	Long-pec to Day 4	whole organism viability, abnormal	Fig. 1
WT	chemical treatment by environment: doxorubicin	Protruding-mouth	atrium decreased thickness, abnormal	Fig. 1
WT	chemical treatment by environment: doxorubicin	Protruding-mouth	atrium elongated, abnormal	Fig. 1
WT	chemical treatment by environment: doxorubicin	Protruding-mouth	cardiac ventricle condensed, abnormal	Fig. 1
WT	chemical treatment by environment: doxorubicin	Protruding-mouth	pericardium edematous, abnormal	Fig. 1
WT	chemical treatment by injection: doxorubicin	Adult	cardiac ventricle Ab11-map1lc3 labeling decreased amount, abnormal	Fig. 3
WT	chemical treatment by injection: doxorubicin	Adult	heart atg7 expression decreased amount, abnormal	Fig. 3
WT	chemical treatment by injection: doxorubicin	Adult	heart nppa expression increased amount, abnormal	Fig. 2
WT	chemical treatment by injection: doxorubicin	Adult	heart nppb expression increased amount, abnormal	Fig. 2

1 - 10 of 24

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab3-gapdh	polyclonal		IgG	Rabbit
Ab11-map1lc3	monoclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Mapping

Lu et al., 2021 ZDB-PUB-210326-1 PMID:33761601

Calycosin attenuates doxorubicin-induced cardiotoxicity via autophagy regulation in zebrafish models

Lu et al., 2021

ZDB-PUB-210326-1
PMID:33761601